1. Field of the Invention
The invention relates to a process for the preparation of butyl 2-phenylcyclopropanecarboxylates (=BPCP) of the formula (1) and the corresponding amide (2) by reaction of 5-phenylbutyrolactone (3) with hydrogen chloride and a butyl alcohol to give a 4-chloro-4-phenylbutanoic ester (=CPBE) of the formula (4) and subsequent cyclization with an alcoholate to give (1) and reaction with ammonia to give amide (2). ##STR1##
2. Description of the Background
Syntheses of 4-chloro-4-phenylbutanoic esters and 2-phenylcyclopropanecarboxylic esters starting from 5-phenylbutyrolactone, which is easily accessible by reaction of acrylic acid with benzyl alcohol, are known from the literature.
Thus, as early as 1960, U. and S. Julia and B. Bemont described two syntheses of ethyl 4-chloro-4-phenylbutanoate and ethyl 2-phenylcyclopropanecarboxylate starting from 5-phenylbutyrolactone (Bull. Soc. Chim. France 1960, 304-12). In method A, a solution of (3) is dissolved in ethanol, saturated with hydrogen chloride, allowed to stand for 48 hours, poured onto ice water, extracted with ether and worked up by distillation. The yield is only 66%.
In method B, (3) is first reacted with thionyl chloride, the reaction product is added to a solution of hydrogen chloride in ethanol and worked up by distillation. A very high yield of 97% is obtained. The 2nd step, the ring formation, is carried out using sodium tert.-amylate in benzene over a period of 35 hours. The workup is carried out similarly to that in the first step by treatment with ice water, extraction with ether and washing of the ether solutions. Workup by distillation gives the desired product in 77% yield.
These procedures are expensive and lead to many waste products. The use of, for example, thionyl chloride is unfavorable in terms of costs when compared with the use of hydrogen chloride. The use of solid sodium amylate in benzene requires additional costs during preparation of this mixture and workup after the reaction.
For analogous ring closure reactions, R. Lantzsch (Synthesis 1982, 11, 955-956) suggested a cyclization process which operates with the easily handlable aqueous potassium hydroxide solution. However, the disadvantage of this method is the extremely high dilution caused by the required solvent and the use of very large amounts of phase transfer catalysts, which, in terms of weight, amount to more than one-fourth of the weight of the feed material, i.e., the compound analogous to 4. This causes waste water problems and high costs of the feed materials, which by far outweigh the advantages of potassium hydroxide solution.
All the known processes require expensive chemicals, are technically very complex and time-consuming and lead to problems in waste disposal. A process is therefore desirable in which 5-phenylbutyrolactone is converted into a 4-chloro-4-phenylbutanoic ester with hydrogen chloride and an alcohol in a one-pot process and this ester is cyclized without pressure in conventional reactors. The 2-phenylcyclopropanecarboxylic ester obtained can be converted, for example, catalytically to the amide with ammonia.
Such a process, by which butyl 2-phenylcyclopropanecarboxylate can be prepared from 5-phenylbutyrolactone and, if desired, 2-phenylcyclopropanecarboxyamide can be prepared from this ester in a technically simple manner and without the use of expensive reagents, is of great interest, since these products are important raw materials for pharmaceutical products.